Mri contrast agent including t1 contrast material coated on surface of nanoparticle support

Abstract

A magnetic resonance imaging (MRI) T1 contrast agent composition including T1 contrast material coated on the surface of a nanoparticle support and an imaging method using the MRI T1 contrast agent. The MRI T1 contrast agent composition has excellent T1 spin magnetic relaxation effects by modifying the paramagnetic T1 contrast material on the nanoparticle support having a certain diameter such that the paramagnetic T1 contrast material has a certain thickness or less, and thereby remarkably increasing the surface-to-volume ratio of the T1 contrast material. The MRI T1 contrast agent provides more precise and clear T1 positive contrast images, and is thus useful for highly reliable image diagnosis.

1 . A method of synthesizing a magnetic resonance imaging (MRI) T1 contrast agent, with a T1 relaxivity coefficient (r 1 ) value ranging from approximately 1 mM −1 s −1  to 5 mM −1 s −1  at 1.5 Tesla,
 (1) preparing a non-magnetic nanoparticle support comprising SiO 2 , a polysaccharide, or a protein, the diameter of which is 2 to 40 nm wherein a surface of the nanoparticle support comprises surface functional groups, and   (2) forming the paramagnetic metal oxide coating layer having paramagnetic metal oxide bound by coordination bond to the surface functional groups of the non-magnetic nanoparticle support, by a reaction in an aqueous colloidal solution in which the non-magnetic nanoparticle support is dispersed, while adjusting (i) the ratio of the thickness of the paramagnetic metal oxide coating layer to the diameter of the non-magnetic nanoparticle support to 1:25 to 1:6 and (ii) the thickness of the paramagnetic metal oxide coating layer to 0.1 to 1 nm.   
     
     
         2 . The synthesizing method of  claim 1 , wherein the T1 contrast agent shortens T1 relaxation time (spin-lattice relaxation time) to induce a positive contrast on T1-weighted images without inducing a negative contrast associated with a T2 contrast agent. 
     
     
         3 . The synthesizing method of  claim 2 , wherein the T1-weighted images obtained in MRI scan provide an information on body parts or an information for medical diagnosis. 
     
     
         4 . The synthesizing method of  claim 3 , wherein the body parts are blood vessels. 
     
     
         5 . The synthesizing method of  claim 4 , wherein the information on body parts is the presence or absence of bleeding in a lesion. 
     
     
         6 . The synthesizing method of  claim 1 , wherein metal ion (M n+ ) in the paramagnetic metal oxide is Ti n+ , V n+ , Cr n+ , Mn n+ , Fe n+ , Co n+ , Ni n+ , Cu n+ , Ru n+  (0<n≥14) or a lanthanide metal. 
     
     
         7 . The synthesizing method of  claim 1 , wherein the polysaccharide is a dextran. 
     
     
         8 . A T1 contrast agent with a T1 relaxivity coefficient (r 1 ) value ranging from approximately 1 mM −1 s −1  to 5 mM −1 s −1  at 1.5 Tesla, which is prepared by the method of  claim 1 .
 wherein the T1 contrast agent comprising   (i) a non-magnetic nanoparticle support comprising SiO 2 , a polysaccharide, or a protein wherein a surface of the nanoparticle support comprises surface functional groups, and   (ii) a paramagnetic metal oxide coating layer having paramagnetic metal oxide bound by coordination bond to the surface functional groups,   wherein a ratio of thickness of the paramagnetic metal oxide coating layer to a diameter of the non-magnetic nanoparticle support is to 1:25 to 1:6; the diameter of the non-magnetic nanoparticle support is 2 to 40 nm; and the thickness of the paramagnetic metal oxide coating layer is 0.1 to 1 nm.   
     
     
         9 . The T1 contrast agent of  claim 8 , wherein the T1 contrast agent shortens T1 relaxation time (spin-lattice relaxation time) to induce a positive contrast on T1-weighted images without inducing a negative contrast associated with a T2 contrast agent. 
     
     
         10 . The T1 contrast agent of  claim 9 , wherein the T1-weighted images obtained in MRI scan provide an information on body parts or an information for medical diagnosis. 
     
     
         11 . The T1 contrast agent of  claim 10 , wherein the body parts are blood vessels. 
     
     
         12 . The T1 contrast agent of  claim 11 , wherein the information on body parts is the presence or absence of bleeding in a lesion. 
     
     
         13 . The T1 contrast agent of  claim 8 , wherein metal ion (M n+ ) in the paramagnetic metal oxide is Ti n+ , V n+ , Cr n+ , Mn n+ , Fe n+ , Co n+ , Ni n+ , Cu n+ , Ru n+  (0<n≥14) or a lanthanide metal. 
     
     
         14 . The T1 contrast agent of  claim 8 , wherein the polysaccharide is a dextran.